A large increase in anti-melanoma-differentiation-associated-gene-5 (mda5) antibody positivity and associated disease in yorkshire since 2020

Background Melanoma differentiation-associated protein 5 (MDA5) is an intracellular detector of viral RNA. It is considered that viral infections are involved in the aetiology of autoimmune diseases, including autoimmune myositis. Previously we reported on a post-COVID-19 pandemic cluster of myositis occurring in the Yorkshire region (De Marco, 2022), despite the usually low frequency observed in the UK. More recently, we noticed increased anti-MDA5 positivity rate in myoblot tests. Objectives Our aim is to appraise the significance of the observed increased anti-MDA5 positivity recognized at our tertiary centre. Methods The Leeds Teaching Hospitals NHS Trust serves as an immunology laboratory reference for the wider Yorkshire region (3.6 million residents). We audited the increased anti-MDA5 positivity in relationship to other muscle-specific autoantibodies (Euroimmun immunoblot©) analysing retrospectively all tests performed between January 2018 and December 2022. Clinical notes review focused on: MDA5+ without disease; patterns of symptomatic MDA5 disease (including degree of ILD); muscle or other organs involvement; response to therapy. We also appraised the temporal associations between recent COVID-19 infection and SARS-CoV-2 vaccination. Results Requests for anti-MDA5 were stable between 2018 and 2020, but doubled thereafter. Anti-MDA5 positivity went from 0.6% to 4.9% in that period, dropping to 2.2% at the end of 2022 (Figure 1). Out of 66 individuals testing positive for anti-MDA5, clinical notes were available in 50 cases. Eleven had myositis without ILD (7 had dermatomysitis/”mechanic” hands rash). 18/50 cases developed ILD (12 had also myositis associated pathology, including 5 dermatomyositis rash and 5 “mechanic” hands). No cases of carditis were recorded. After treatment, outcome was stable/improved in 17 cases (6 ILD cases). Yet, 3 cases worsened and 6 died despite therapy (ILD cases). Twenty cases had signs described as within the connective tissues diseases spectrum (without any lung involvement), though no formal diagnosis. A minority of cases were associated with evidence of SARS-CoV-2 infection or vaccination, with 15 cases vaccinated before disease onset and 4 with preceding COVID-19 infection. Figure 1. Conclusion Our data show an increased rate of anti-MDA5 positivity in the latter stages of the COVID-19 pandemic, as previously noted in the UK (Hannah J, ACR 2022). Most cases had MDA5 positivity without confirmed autoimmune disease and despite the MDA5 positivity occurrence in the face of the COVID-19 pandemic further longitudinal observation is needed to ascertain any potential links with either infection, vaccination or both. References [1]DeMarco G, et al Vaccines (Basel) 2022; 10: 1184. [2]Hannah J, et al. ACR Convergence Meeting 2022; Abstract Number: 1857 Acknowledgements: NIL. Disclosure of Interests None Declared.